Is there any evidence that weaknesses don't make a difference? I'd say that there's some suggestion they do - each time weaknesses have been triggered the epic seems to become uncertain, even regretful in some cases we've seen. They just generally don't live long enough, or have the weakness triggered long enough, for us to actually see any psychological change.
As to Calamity - that seems to be assuming that Calamity chooses what powers and weakness to give someone, rather than simply empowering them and their own mind/body sorting out how the power is then expressed (or not expressed as the case may be). All we've had on the powers that Calamity grants is that they're thematically appropriate, but that might not be a choice of his.
I also think he's got a somewhat different, and even possibly nobler (but more cowardly) motivation than simply trying to corrupt people and cause damage - but that's for elsewhere.
